Genetic determinants of plasma protein levels in the Estonian population.
Details
Serval ID
serval:BIB_2ED69D7E6C4B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genetic determinants of plasma protein levels in the Estonian population.
Journal
Scientific reports
Working group(s)
Estonian Biobank Research Team
Contributor(s)
Metspalu A., Milani L., Nelis M., Hudjashov G.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
02/04/2024
Peer-reviewed
Oui
Editor
Metspalu A Milani L. Nelis M. Hudjashov G., Estonian Biobank Research Team
Volume
14
Number
1
Pages
7694
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Abstract
The proteome holds great potential as an intermediate layer between the genome and phenome. Previous protein quantitative trait locus studies have focused mainly on describing the effects of common genetic variations on the proteome. Here, we assessed the impact of the common and rare genetic variations as well as the copy number variants (CNVs) on 326 plasma proteins measured in up to 500 individuals. We identified 184 cis and 94 trans signals for 157 protein traits, which were further fine-mapped to credible sets for 101 cis and 87 trans signals for 151 proteins. Rare genetic variation contributed to the levels of 7 proteins, with 5 cis and 14 trans associations. CNVs were associated with the levels of 11 proteins (7 cis and 5 trans), examples including a 3q12.1 deletion acting as a hub for multiple trans associations; and a CNV overlapping NAIP, a sensor component of the NAIP-NLRC4 inflammasome which is affecting pro-inflammatory cytokine interleukin 18 levels. In summary, this work presents a comprehensive resource of genetic variation affecting the plasma protein levels and provides the interpretation of identified effects.
Keywords
Humans, Genome-Wide Association Study, Proteome/genetics, Estonia, Polymorphism, Single Nucleotide, Quantitative Trait Loci/genetics, Blood Proteins/genetics, DNA Copy Number Variations/genetics
Pubmed
Web of science
Open Access
Yes
Create date
08/04/2024 13:16
Last modification date
09/08/2024 14:57